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ORTHOMYXO
VIRUS
• Case Study
• Introduction
• Structure
• HN Terminology
• Specific Proteins
• Characteristics
• Types
• Antigenic variation (antigenic shift antigenic drift)
• Morphology
• Replication
• Pathogenesis
• Transmission
• Laboratory Diagnosis
• Treatment
• Avian inluenza virus
• Vaccine
• Preventions of Influenza virus
CONTENTS
4
• A22-year old man suddenly experienced
headache, malaise, dry cough and fever.
He basically felt “lousy”. After a couple
of days, he had a sore throat, his cough
had worsened, and he started to feel
nauseated and vomited. Several of his
family members had experienced similar
symptoms during the previous two weeks.
Case Study 3
• Influenza virus infections have become such a common
and integral part of our lives that any respiratory infection
that causes discomfort is typically referred to as an
episode of flu.
• In reality, most of these infections are probably not caused
by influenza viruses but by more benign agents.
• True influenza virus infections can pose a serious threat.
• Influenza virus infection in humans occurs in seasonal
epidemics and is estimated to result in up to 5 million
cases of serious disease with 250,000–500,000 deaths.
Introduction 4
5
• Spherical/ filamentous
• Enveloped
• Single, segmented RNA enclosed in a
protein capsid.
• Capsid surrounded by lipoprotein
envelope.
• Two glycoproteins _Neuraminidase and
Haemaggutination are present.
Structure 6
7
8
9
HN Terminology 10
• H refers to Haemagglutinnin types and each is
given a number H1, H2 etc
• Neuraminidase is designated N and different
forms are available as well e.g. H5N1 (avian) and
H1N1 (swine).
• Different combinations of H and N
glycoproteins give rise to different strains
Haemugglutination 11
• Act with red cells of different species
• Type A and B – RBC's of Fowl, Human
and pigs
• Type C only RBC's of Fowl.
Types Of
Haemugglutinnin
12
• Haemagglutination is strain specific.
• Great variations.
• HA there are 15 subtypes H1 to H15
in avian influenza.
• But only 4 variants in humans.
Neuraminidase 13
• Neuraminidase are glycoproteins
• Destroys cell receptors by hydrolysis
cleavage.
• There are nine different subtypes
N1 – N9.
Two specific proteins used to differentiate among
influenzaA,B and C viruses
➢Matrix protein(M1)
• viral structure protein.
• Interacts with nucleocapsid and envelope.
• Promotes assembly.
➢Membrane protein(M2)
• Forms membrane channel
• Facilitates uncoating and HAproduction.
Specific Proteins 14
• Influenza A, B and C the only members.
• Enveloped virion; inactivated by
detergents.
• Segmented negative- sense RNAgenome
with eight nucleocapsid segments.
• Genetic instability responsible for annual
epidemics (mutation:drift) and periodic
pandemics (reassortment:shift).
Characteristics 15
• The family Orthomyxoviridae contains three
genera (or types):
• Influenzavirus A, B, and C.
• They are distinguished by their antigenically
distinct nucleoprotein (NP) and matrix (M)
proteins.
• Influenza type A& B are significant human
pathogens influenza while type C is less
important. TypeAinfluenza infect human as well
as animals.
Types 16
• Unique feature of this virus lies with antigenic
variation.
• High in typeAvirus
• Less in type B virus
• Not in type C virus
• RNPand matrix protein are stable
• Hemagglutination and Neuraminidase are
independent of the variations.
Antigenic Variation 17
• MinorAg changes in HA/NA/both
• Gradual
• Regular intervals
• Mutation in HA/NAgenes
• Epidemics
Antigenic Drift 18
• Major changes in HA(2-3), NA(1-3)
• New subtype (unrelated to old virus)
• Unlikely due to mutation.
• Gene assortment (recombination)
• Major epidemics, pandemics.
Antigenic Shift 19
20
21
Morphology Of Influenza
Virus
22
• Virions are spherical, between 80nm-120nm
in diameter, helical symmetry, enveloped with
spikes.
• About 80% of the spikes are hemagglutinin
antigen and the remainder are neuraminidase.
There is a layer of matrix protein which
encloses the (-) ss-RNAgenome of the virus.
• RNAis associated with nucleoprotein.
Morphology 23
• The genome is composed of eight fragments
complexed with protein to form
ribonucleoprotein arranged in helix.
• Hemagglutinin “HA” is a rod-shaped
glycoprotein with triangular cross section.
• It agglutinates erythrocytes, and plays an
important role in the attachment and entry of
the virus to host cells and in determining
virulence.
• Host cell protease cleaves HAinto two
molecules; HA1 and HA2; a necessary step for
infection.
24
• The neuraminidase “NA” is an enzyme which
destroys neuraminic acid “sialic acid”, a
component of the specific cell receptors for the
virus.
• Its main function is in the release of new virus
from cells.
• NAis a glycoprotein, its spikes look like
mushrooms.
• Inside the matrix shell are the nucleoprotein
and an RNAtranscriptase, that is essential for
replication.
25
• Endocytosis: engulfment of virion into vacuoles (endosomes),
acidic pH induces a change in the configuration of the HA.
• Uncoating.
• Virus RNAis transported to the cell nucleus
• Transcription by virus RNAtranscriptase to complementary (+)
strand that can function as mRNA
• It also serves as template for the Synthesis of negative RNA
strands for new virions.
• Translation, in host cell cytoplasm, to produce viral proteins.
• The new virions are assembled at the host cell surface
membrane.
• Budding and release
Replication 26
27
Pathogenesis
• Infection is acquired by the respiratory route
causing upper respiratory tract infection.
• Virus multiplies in the epithelium and destroys the
cilia, followed by transient viremia.
• Complications may include
secondary bacterial infection, Reye’s
syndrome
• Reye’s syndrome
• A rare but potentially fatal disease of the liver,
children with fever due to influenza
especially type B should
syndrome.
avoid taking aspirin as this may lead to
Reye's
• Incubation period 2-3 days.
• Symptoms may include:
• shivering
• headache
• malaise
• and aching in the limbs and back.
• The temperature rises rapidly to around 39 ºC.
• The severity of influenza is proportional to age.
29
Transmission of
Influenza Virus
30
• Transmission mainly person to person by
sneezing, coughing or by simply talking.
• Virus likes a cool, less humid atmosphere
(winter heating season).
• Extensively spread by school children.
• The respiratory tract is the gate opening of the
virus.
• Influenza can also be transmitted by saliva,
nasal secretion, feces and blood.
Transmission Of
Influenza virus
31
32
33
• Immunofluorescence staining of cells in
nasopharyngeal aspirates.
• Virus isolation from throat or nasal swabs,
using chick embryo or cell culture.
• Hemagglutination test or hemagglutination
inhibition.
• Serological testing for specific antibodies.
• RT-PCR
Laboratory Diagnosis 34
• Acetaminophen, antihistamines and other drugs
are used to relieve the symptoms.
• Amantadine and rimantadine inhibit an
uncoating step of influenzaAvirus but do not
affect the influenza B and C virus.
• Zanamivir and oseltamivir inhibit bothAand B
as enzyme inhibitor of neuraminidase.
Treatment Of Influenza
virus
35
• Avian influenza virus occurs naturally among
birds.
• Wild birds carry viruses in their intestine but
usually do not get sick of them.
• The virus is very contagious among birds and can
make some domesticated birds including chickens,
ducks and turkeys very sick and kill them.
• Infected birds shed the virus in their saliva, nasal
secretions and feces.
Avian influenza Virus
(Bird Flu),H5N1
36
• The highly pathogenic form of the virus spreads
more rapidly through flocks of poultry, it may
affect multiple internal organs and has a mortality
rate that can reach % often within 48 hours.
• Infection with H5N1 influenza can occur in
humans.
• Infection results from contact with infected
poultry e.g domesticated chickens, ducks and
turkey.
• Infection from one ill person to another is rare.
Avian influenza Virus
(Bird Flu),H5N1
37
• Symptoms in humans have ranged:
• Influenza-like symptoms (fever, cough, sore throat
and muscle aches).
• Eye infections.
• Pneumonia and severe respiratory diseases
• and other life threatening complications
e.g respiratory failure.
• Some virulent influenza strains can escape innate and
adaptive immunity via NS1 protein (nonstructural
protein).
Avian influenza Virus
(Bird Flu),H5N1
38
• Elimination of infected birds.
• Careful dealings with birds.
• Restriction of poultry and egg import.
• Administration of antiviral drugs.
• Vaccine is available.
Preventions Of Influenza
Virus
39
40
41
• Personal hygiene.
• Aeration of living and work places.
• Sneezing and coughing using tissue paper and
disposing it immediately.
• Bed rest of infected persons
• Avoid contact with infected persons.
• Antiviral drugs (e.g Neuraminidase inhibitors)
• Vaccine is available.
Control 42
43
44

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orthomyxovirus slides

  • 2. • Case Study • Introduction • Structure • HN Terminology • Specific Proteins • Characteristics • Types • Antigenic variation (antigenic shift antigenic drift) • Morphology • Replication • Pathogenesis • Transmission • Laboratory Diagnosis • Treatment • Avian inluenza virus • Vaccine • Preventions of Influenza virus CONTENTS 4
  • 3. • A22-year old man suddenly experienced headache, malaise, dry cough and fever. He basically felt “lousy”. After a couple of days, he had a sore throat, his cough had worsened, and he started to feel nauseated and vomited. Several of his family members had experienced similar symptoms during the previous two weeks. Case Study 3
  • 4. • Influenza virus infections have become such a common and integral part of our lives that any respiratory infection that causes discomfort is typically referred to as an episode of flu. • In reality, most of these infections are probably not caused by influenza viruses but by more benign agents. • True influenza virus infections can pose a serious threat. • Influenza virus infection in humans occurs in seasonal epidemics and is estimated to result in up to 5 million cases of serious disease with 250,000–500,000 deaths. Introduction 4
  • 5. 5
  • 6. • Spherical/ filamentous • Enveloped • Single, segmented RNA enclosed in a protein capsid. • Capsid surrounded by lipoprotein envelope. • Two glycoproteins _Neuraminidase and Haemaggutination are present. Structure 6
  • 7. 7
  • 8. 8
  • 9. 9
  • 10. HN Terminology 10 • H refers to Haemagglutinnin types and each is given a number H1, H2 etc • Neuraminidase is designated N and different forms are available as well e.g. H5N1 (avian) and H1N1 (swine). • Different combinations of H and N glycoproteins give rise to different strains
  • 11. Haemugglutination 11 • Act with red cells of different species • Type A and B – RBC's of Fowl, Human and pigs • Type C only RBC's of Fowl.
  • 12. Types Of Haemugglutinnin 12 • Haemagglutination is strain specific. • Great variations. • HA there are 15 subtypes H1 to H15 in avian influenza. • But only 4 variants in humans.
  • 13. Neuraminidase 13 • Neuraminidase are glycoproteins • Destroys cell receptors by hydrolysis cleavage. • There are nine different subtypes N1 – N9.
  • 14. Two specific proteins used to differentiate among influenzaA,B and C viruses ➢Matrix protein(M1) • viral structure protein. • Interacts with nucleocapsid and envelope. • Promotes assembly. ➢Membrane protein(M2) • Forms membrane channel • Facilitates uncoating and HAproduction. Specific Proteins 14
  • 15. • Influenza A, B and C the only members. • Enveloped virion; inactivated by detergents. • Segmented negative- sense RNAgenome with eight nucleocapsid segments. • Genetic instability responsible for annual epidemics (mutation:drift) and periodic pandemics (reassortment:shift). Characteristics 15
  • 16. • The family Orthomyxoviridae contains three genera (or types): • Influenzavirus A, B, and C. • They are distinguished by their antigenically distinct nucleoprotein (NP) and matrix (M) proteins. • Influenza type A& B are significant human pathogens influenza while type C is less important. TypeAinfluenza infect human as well as animals. Types 16
  • 17. • Unique feature of this virus lies with antigenic variation. • High in typeAvirus • Less in type B virus • Not in type C virus • RNPand matrix protein are stable • Hemagglutination and Neuraminidase are independent of the variations. Antigenic Variation 17
  • 18. • MinorAg changes in HA/NA/both • Gradual • Regular intervals • Mutation in HA/NAgenes • Epidemics Antigenic Drift 18
  • 19. • Major changes in HA(2-3), NA(1-3) • New subtype (unrelated to old virus) • Unlikely due to mutation. • Gene assortment (recombination) • Major epidemics, pandemics. Antigenic Shift 19
  • 20. 20
  • 21. 21
  • 23. • Virions are spherical, between 80nm-120nm in diameter, helical symmetry, enveloped with spikes. • About 80% of the spikes are hemagglutinin antigen and the remainder are neuraminidase. There is a layer of matrix protein which encloses the (-) ss-RNAgenome of the virus. • RNAis associated with nucleoprotein. Morphology 23
  • 24. • The genome is composed of eight fragments complexed with protein to form ribonucleoprotein arranged in helix. • Hemagglutinin “HA” is a rod-shaped glycoprotein with triangular cross section. • It agglutinates erythrocytes, and plays an important role in the attachment and entry of the virus to host cells and in determining virulence. • Host cell protease cleaves HAinto two molecules; HA1 and HA2; a necessary step for infection. 24
  • 25. • The neuraminidase “NA” is an enzyme which destroys neuraminic acid “sialic acid”, a component of the specific cell receptors for the virus. • Its main function is in the release of new virus from cells. • NAis a glycoprotein, its spikes look like mushrooms. • Inside the matrix shell are the nucleoprotein and an RNAtranscriptase, that is essential for replication. 25
  • 26. • Endocytosis: engulfment of virion into vacuoles (endosomes), acidic pH induces a change in the configuration of the HA. • Uncoating. • Virus RNAis transported to the cell nucleus • Transcription by virus RNAtranscriptase to complementary (+) strand that can function as mRNA • It also serves as template for the Synthesis of negative RNA strands for new virions. • Translation, in host cell cytoplasm, to produce viral proteins. • The new virions are assembled at the host cell surface membrane. • Budding and release Replication 26
  • 27. 27
  • 28. Pathogenesis • Infection is acquired by the respiratory route causing upper respiratory tract infection. • Virus multiplies in the epithelium and destroys the cilia, followed by transient viremia. • Complications may include secondary bacterial infection, Reye’s syndrome • Reye’s syndrome • A rare but potentially fatal disease of the liver, children with fever due to influenza especially type B should syndrome. avoid taking aspirin as this may lead to Reye's
  • 29. • Incubation period 2-3 days. • Symptoms may include: • shivering • headache • malaise • and aching in the limbs and back. • The temperature rises rapidly to around 39 ºC. • The severity of influenza is proportional to age. 29
  • 31. • Transmission mainly person to person by sneezing, coughing or by simply talking. • Virus likes a cool, less humid atmosphere (winter heating season). • Extensively spread by school children. • The respiratory tract is the gate opening of the virus. • Influenza can also be transmitted by saliva, nasal secretion, feces and blood. Transmission Of Influenza virus 31
  • 32. 32
  • 33. 33
  • 34. • Immunofluorescence staining of cells in nasopharyngeal aspirates. • Virus isolation from throat or nasal swabs, using chick embryo or cell culture. • Hemagglutination test or hemagglutination inhibition. • Serological testing for specific antibodies. • RT-PCR Laboratory Diagnosis 34
  • 35. • Acetaminophen, antihistamines and other drugs are used to relieve the symptoms. • Amantadine and rimantadine inhibit an uncoating step of influenzaAvirus but do not affect the influenza B and C virus. • Zanamivir and oseltamivir inhibit bothAand B as enzyme inhibitor of neuraminidase. Treatment Of Influenza virus 35
  • 36. • Avian influenza virus occurs naturally among birds. • Wild birds carry viruses in their intestine but usually do not get sick of them. • The virus is very contagious among birds and can make some domesticated birds including chickens, ducks and turkeys very sick and kill them. • Infected birds shed the virus in their saliva, nasal secretions and feces. Avian influenza Virus (Bird Flu),H5N1 36
  • 37. • The highly pathogenic form of the virus spreads more rapidly through flocks of poultry, it may affect multiple internal organs and has a mortality rate that can reach % often within 48 hours. • Infection with H5N1 influenza can occur in humans. • Infection results from contact with infected poultry e.g domesticated chickens, ducks and turkey. • Infection from one ill person to another is rare. Avian influenza Virus (Bird Flu),H5N1 37
  • 38. • Symptoms in humans have ranged: • Influenza-like symptoms (fever, cough, sore throat and muscle aches). • Eye infections. • Pneumonia and severe respiratory diseases • and other life threatening complications e.g respiratory failure. • Some virulent influenza strains can escape innate and adaptive immunity via NS1 protein (nonstructural protein). Avian influenza Virus (Bird Flu),H5N1 38
  • 39. • Elimination of infected birds. • Careful dealings with birds. • Restriction of poultry and egg import. • Administration of antiviral drugs. • Vaccine is available. Preventions Of Influenza Virus 39
  • 40. 40
  • 41. 41
  • 42. • Personal hygiene. • Aeration of living and work places. • Sneezing and coughing using tissue paper and disposing it immediately. • Bed rest of infected persons • Avoid contact with infected persons. • Antiviral drugs (e.g Neuraminidase inhibitors) • Vaccine is available. Control 42
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  • 44. 44